A class of N-arylalkyl-1-(alkyl or aralkyl)-2-acylaminoalkyl-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamides are inhibitors of the HIV integrase enzyme. More particularly, these compounds can inhibit the HIV type 1 (HIV-1) integrase enzyme and the HIV type 2 (HIV-2) integrase enzyme. This class includes the compounds of Formula I as defined and described below. These compounds and pharmaceutically acceptable salts thereof are useful in the treatment or prophylaxis of infection by HIV and in the treatment, prophylaxis, or delay in the onset or progression of AIDS. Representative compounds of this class are described in International Publication No. WO 03/035077 and in corresponding U.S. Pat. No. 7,169,780. Among the compounds disclosed in WO 03/035077 is N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(1-methyl-1-{[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino}ethyl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide, hereinafter referred to as Compound A. The generic name of Compound A is raltegravir, and raltegravir potassium is the active ingredient in ISENTRESS (Merck & Co., Inc.) which is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in treatment-experienced adult patients with evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents. The structure of Compound A is as follows:

US 2006/0122205 and corresponding WO 2006/060730 disclose a method that can be employed to prepare compounds of the above-described class. The method involves (i) alkylating an alkyl 2-[(protected amino)alkyl]-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate to obtain alkyl 2-[(protected amino)alkyl]-1-alkyl-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylate, (ii) coupling the product of step i with an aralkylamine to obtain N-aralkyl 2-[(protected amino)alkyl]-1-alkyl-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide, (iii) deprotecting the 2-aminoalkyl group in the product of step ii to obtain N-aralkyl 2-aminoalkyl-1-alkyl-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxamide, and (iv) acylating the 2-aminoalkyl group with a suitable acylating agent to obtain a compound of the class. The preparation of Compound A as described in US 2006/0122205 is representative:

WO 03/035077 discloses processes related to the process described in US 2006/0122205 including a preparation of Compound A (see Steps 4, 5, 6, (no step 7), 8 and 9 of Example 18 and Example 19):

The routes described above are practical routes for the preparation of Compound A and related hydroxypyrimidinone carboxamides. In particular, the route described US 2006/0122205 can be employed for the large-scale production of Compound A. Nonetheless, there is always a need for alternative preparative routes which, for example, use reagents that are less expensive and/or easier to handle, consume smaller amounts of reagents, provide a higher yield of product, involve fewer steps, have smaller and/or more eco-friendly waste products, and/or provide a product of higher purity.